Skip to main content

Advertisement

SpringerLink
Log in

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aarsland D, Andersen K, Larsen JP et al (2003) Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 60:387–392

    Article  PubMed  Google Scholar 

  2. Aarsland D, Kurz MW (2010) The epidemiology of dementia associated with Parkinson disease. J Neurol Sci 289:18–22

    Article  PubMed  Google Scholar 

  3. Alves G, Larsen JP, Emre M et al (2006) Changes in motor subtype and risk for incident dementia in Parkinson’s disease. Mov Disord 21:1123–1130

    Article  PubMed  Google Scholar 

  4. Alves G, Brønnick K, Aarsland D et al (2010) CSF amyloid-beta and tau proteins, and cognitive performance, in early and untreated Parkinson’s disease: the Norwegian ParkWest study. J Neurol Neurosurg Psychiatry 81:1080–1086

    Article  PubMed  Google Scholar 

  5. Alves G, Lange J, Blennow K et al (2014) CSF Aβ42 predicts early-onset dementia in Parkinson disease. Neurology 82:1784–1790

    Article  CAS  PubMed  Google Scholar 

  6. Compta Y, Parkkinen L, O’Sullivan SS et al (2011) Lewy- and Alzheimer-type pathologies in Parkinson’s disease dementia: which is more important? Brain 134:1493–1505

    Article  PubMed  PubMed Central  Google Scholar 

  7. Duka T, Duka V, Joyce JN, Sidhu A (2009) α-Synuclein contributes to GSK-3β-catalyzed tau phosphorylation in Parkinson’s disease model. FASEB J 23:2820–2830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Giasson BI, Forman MS, Higuchi M et al (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300:636–640

    Article  CAS  PubMed  Google Scholar 

  9. Gomperts SN, Locascio JJ, Rentz D et al (2013) Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia. Neurology 80:85–91

    Article  PubMed  PubMed Central  Google Scholar 

  10. Guo JL, Covell DJ, Daniels JP et al (2013) Distinct α-synuclein strains differentially promote tau inclusions in neurons. Cell 154:103–117

    Article  CAS  PubMed  Google Scholar 

  11. Halliday GM, Holton JL, Revesz T, Dickson DW (2011) Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol 122:187–204

    Article  CAS  PubMed  Google Scholar 

  12. Hobson P, Meara J (2004) Risk and incidence of dementia in a cohort of older subjects with Parkinson’s disease in the United Kingdom. Mov Disord 19:1043–1049

    Article  PubMed  Google Scholar 

  13. Hughes TA, Ross HF, Musa S et al (2000) A 10-year study of the incidence of and factors predicting dementia in Parkinson’s disease. Neurology 54:1596–1602

    Article  CAS  PubMed  Google Scholar 

  14. Irwin DJ, White MT, Toledo JB et al (2012) Neuropathologic substrates of Parkinson disease dementia. Ann Neurol 72:587–598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Irwin DJ, Lee VM, Trojanowski JQ (2013) Parkinson’s disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies. Nat Rev Neurosci 14:626–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jankovic J, McDermott M, Carter J et al (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. Neurology 40:1529–1534

    Article  CAS  PubMed  Google Scholar 

  17. Jellinger KA (1999) Post mortem studies in Parkinson’s disease-is it possible to detect brain areas for specific symptoms? J Neural Transm Suppl 56:1–29

    Article  CAS  PubMed  Google Scholar 

  18. Kang JH, Irwin DJ, Chen-Plotkin AS et al (2013) Association of cerebrospinal fluid β-amyloid 1-42, t-tau, p-tau181, and α-synuclein levels with clinical features of drug-naïve patients with early Parkinson disease. JAMA Neurol 70:1277–1287

    PubMed  PubMed Central  Google Scholar 

  19. Levy G, Tang MX, Louis ED et al (2002) The association of incident dementia with mortality in PD. Neurology 59:1708–1713

    Article  CAS  PubMed  Google Scholar 

  20. Lewis SJG, Foltynie T, Blackwell AD et al (2005) Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 76:343–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mata IF, Leverenz JB, Weintraub D et al (2014) APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA Neurol 71:1405–1412

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mollenhauer B, Locascio JJ, Schulz-Schaeffer W et al (2011) α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurol 10:230–240

    Article  CAS  PubMed  Google Scholar 

  23. Montine TJ, Shi M, Quinn JF et al (2010) CSF Aβ42 and tau in Parkinson’s disease with cognitive impairment. Mov Disord 25:2682–2685

    Article  PubMed  PubMed Central  Google Scholar 

  24. Nalls MA, Pankratz N, Lill CM et al (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet 46:989–993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Parashos SA, Swearingen CJ, Biglan KM et al (2009) Determinants of the timing of symptomatic treatment in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience. Arch Neurol 66:1099–1104

    Article  PubMed  PubMed Central  Google Scholar 

  26. Parashos SA, Luo S, Biglan KM et al (2014) Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience. JAMA Neurol 71:710–716

    Article  PubMed  PubMed Central  Google Scholar 

  27. Initiative Parkinson Progression Marker (2011) The Parkinson Progression Marker Initiative (PPMI). Prog Neurobiol 95:629–635

    Article  Google Scholar 

  28. Parnetti L, Tiraboschi P, Lanari A et al (2008) Cerebrospinal fluid biomarkers in Parkinson’s disease with dementia and dementia with Lewy bodies. Biol Psychiatry 64:850–855

    Article  CAS  PubMed  Google Scholar 

  29. Parnetti L, Chiasserini D, Bellomo G et al (2011) Cerebrospinal fluid tau/α-synuclein ratio in Parkinson’s disease and degenerative dementia. Mov Disord 8:1428–1435

    Article  Google Scholar 

  30. Paulus W, Jellinger K (1991) The neuropathologic basis of different clinical subgroups of Parkinson’s disease. J Neuropathol Exp Neurol 50:743–755

    Article  CAS  PubMed  Google Scholar 

  31. Rajput AH, Sitte HH, Rajput A et al (2008) Globus pallidus dopamine and Parkinson motor subtype: clinical and brain biochemical correlation. Neurology 70:1403–1410

    Article  CAS  PubMed  Google Scholar 

  32. Rajput AH, Voll A, Rajput ML et al (2009) Course in Parkinson disease subtypes: a 39-year clinicopathologic study. Neurology 73:206–212

    Article  CAS  PubMed  Google Scholar 

  33. Selikhova M, Williams DR, Kempster PA et al (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132:2947–2957

    Article  CAS  PubMed  Google Scholar 

  34. Shi M, Bradner J, Hancock AM et al (2011) Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol 69:570–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Siderowf A, Xie SX, Hurtig H et al (2010) CSF amyloid β1-42 predicts cognitive decline in Parkinson disease. Neurology 75:1055–1061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Stebbins GT, Goetz CG, Burn DJ et al (2013) How to identify tremor dominant and postural instability/gait difficulty groups with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale: comparison with the Unified Parkinson’s Disease Rating Scale. Mov Disord 28:668–670

    Article  PubMed  Google Scholar 

  37. Toledo JB, Korff A, Shaw LM et al (2013) CSF α-synuclein improves diagnostic and prognostic performance of CSF tau and Aβ in Alzheimer’s disease. Acta Neuropathol 126:683–697

    Article  CAS  PubMed  Google Scholar 

  38. Toledo JB, Gopal P, Raible K et al (2015) Pathological a-synuclein distribution in subjects with coincident Alzheimer’s and Lewy body pathology. Acta Neuropathol (E-pub)

  39. Tsuang D, Leverenz JB, Lopez OL et al (2013) APOE e4 increases risk for dementia in pure synucleinopathies. JAMA Neurol 70:223–228

    Article  PubMed  PubMed Central  Google Scholar 

  40. van de Berg WD, Hepp DH, Dijkstra AA et al (2012) Patterns of α-synuclein pathology in incidental cases and clinical subtypes of Parkinson’s disease. Parkinsonism Relat Disord 18(Suppl 1):S28–S30

    Article  PubMed  Google Scholar 

  41. Williams-Gray CH, Foltynie T, Brayne CEG et al (2007) Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain 130:1787–1798

    Article  CAS  PubMed  Google Scholar 

  42. Williams-Gray CH, Goris A, Saiki M et al (2009) Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s disease. J Neurol 256:493–498

    Article  CAS  PubMed  Google Scholar 

  43. Wills J, Jones J, Haggerty T et al (2010) Elevated tauopathy and alpha-synuclein pathology in postmortem Parkinson’s disease brains with and without dementia. Exp Neurol 225:210–218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The Parkinson’s Progression Markers Initiative Group includes Shirley Lasch; Emily Flagg; Werner Poewe, MD; Todd Sherer, PhD; Claire Meunier; Alice Rudolph, PhD; Cindy Casaceli, MBA; John Seibyl, MD; Susan Mendick, MPH; Norbert Schuff, PhD; Liz Uribe, MS; Jon Yankey, MS; Karen Crawford; Tatiana Foroud, PhD; Paola Casalin, MD, PhD, FRCP; Giulia Malferrari, PhD; Keith Hawkins, PsyD; David Russell, MD, PhD; Laura Leary, BS; Stewart Factor, DO; Barbara Sommerfeld, RN, MSN; Penelope Hogarth, MD; Emily Pighetti; Karen Williams; David Standaert, MD, PhD; Stephanie Guthrie, MSN; Robert Hauser, MD, MBA; Joseph Jankovic, MD; Christine Hunter, RN; Matthew Stern, MD; Abigail Darin; Jim Leverenz, MD; Marne Baca; Sam Frank, MD; Cathi-Ann Thomas, RN, MS; Irene Richard, MD; Cheryl Deeley, MSN; Linda Rees, MPH; Fabienne Sprenger, MD; Wolfgang Oertel, MD; Diana Willeke; Holly Shill, MD; Hubert Fernandez, MD; Jennifer Mule; Daniela Berg, MD; Katharina Gauss; Douglas Galasko, MD; Deborah Fontaine, BSN, MS; Zoltan Mari, MD; Arita McCoy, RN; David Brooks, MD; Bina Shah, BSc; Paolo Barone, MD, PhD; Stuart Isaacson, MD; Angela James; Alberto Espay, MD, MSc; Kristy Espay; Dominic Rowe, MD, PhD; Madelaine Ranola, BN.

The Parkinson’s Progression Markers Initiative Group Affiliations Institute for Neurodegenerative Disorders, New Haven, Connecticut (Lasch, Seibyl, Mendick, Russell, Leary); Clinical Trials Coordination Center, University of Rochester, Rochester, New York (Flagg, Casaceli); Innsbruck Medical University, Innsbruck, Austria (Poewe, Sprenger); The Michael J. Fox Foundation for Parkinson’s Research, New York, New York (Sherer, Meunier); Institute on Aging, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia (Rudolph); University of California, San Francisco (Schuff); University of Iowa, Iowa City (Uribe, Yankey); Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (Crawford); Coriell Institute for Medical Research, Camden, New Jersey (Scutti); BioRep, Milan, Italy (Casalin, Malferrari); Yale University, New Haven, Connecticut (Hawkins); Emory University School of Medicine, Atlanta, Georgia (Factor, Sommerfeld); Oregon Health and Science University, Portland (Hogarth, Pighetti); Northwestern University, Chicago, Illinois (Williams); University of Alabama at Birmingham (Standaert, Guthrie); Baylor College of Medicine, Houston, Texas (Hauser, Jankovic, Hunter); University of Pennsylvania, Philadelphia (Stern, Darin); University of Washington, Seattle (Leverenz, Baca); Boston University, Boston, Massachusetts (Frank, Thomas); University of Rochester, Rochester, New York (Richard, Deeley); Parkinson’s Institute, Sunnyvale, California (Rees); Paracelsus-Elena-Klinik, Kassel, Germany (Oertel, Willeke); Cleveland Clinic, Cleveland, Ohio (Shill, Fernandez, Mule); University of Tuebingen, Tuebingen, Germany (Berg, Gauss); University of California, San Diego (Galasko, Fontaine); Johns Hopkins University, Baltimore, Maryland (Mari, McCoy); Imperial College London, London, England (Brooks, Shah); University of Salerno, Salerno, Italy (Barone); Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, Florida (Isaacson, James); University of Cincinnati, Cincinnati, Ohio (A. Espay, K. Espay); Macquarie University, Sydney, Australia (Rowe, Ranola).

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 7.103 Founders Pavilion 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Ju-Hee Kang, Jon B. Toledo, David J. Irwin, Vivianna Van Deerlin, Teresa Waligórska, Nirali Shah, Sarah Pan, Pawel Zero, John Q. Trojanowski & Leslie M. Shaw

  2. Department of Pharmacology, Hypoxia-related Disease Research Center, Inha University School of Medicine, Incheon, Republic of Korea

    Ju-Hee Kang

  3. Paracelsus-Elena Klinik, Kassel, Germany

    Brit Mollenhauer

  4. Department of Neuropathology and Neurosurgery, University Medical Center Goettingen, Göttingen, Germany

    Brit Mollenhauer

  5. Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA

    Christopher S. Coffey & Chelsea Caspell-Garcia

  6. Center for Neurodegenerative Disease Research, Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Jon B. Toledo, David J. Irwin, Vivianna Van Deerlin, Alice S. Chen-Plotkin, John Q. Trojanowski & Leslie M. Shaw

  7. Department of Neurology, Morris K. Udall Center of Excellence for Parkinson’s Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Daniel Weintraub, David J. Irwin, Alice S. Chen-Plotkin & John Q. Trojanowski

  8. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Daniel Weintraub

  9. Department of Veterans Affairs, Philadelphia, PA, USA

    Daniel Weintraub

  10. Department of Neurosciences, University of California, San Diego, CA, USA

    Douglas R. Galasko

  11. BioLegend Inc., Dedham, MA, USA

    Peggy Taylor

  12. The Michael J. Fox Foundation for Parkinson’s Research, New York, NY, USA

    Mark Frasier & Sohini Chowdhury

  13. Institute for Neurodegenerative Disorders, New Haven, CT, USA

    Kenneth Marek & Danna Jennings

  14. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Karl Kieburtz

  15. University of California-San Francisco and San Francisco Veteran’s Affairs Medical Center, San Francisco, CA, USA

    Caroline M. Tanner

  16. Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Tanya Simuni

  17. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

    Andrew Singleton

  18. Laboratory of Neuro Imaging, The Institute for Neuroimaging and Informatics, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA

    Arthur W. Toga

Authors
  1. Ju-Hee Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brit Mollenhauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christopher S. Coffey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jon B. Toledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel Weintraub
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Douglas R. Galasko
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David J. Irwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vivianna Van Deerlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alice S. Chen-Plotkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chelsea Caspell-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Teresa Waligórska
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Peggy Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Nirali Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Sarah Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Pawel Zero
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mark Frasier
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Kenneth Marek
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Karl Kieburtz
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Danna Jennings
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Caroline M. Tanner
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Tanya Simuni
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Andrew Singleton
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Arthur W. Toga
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Sohini Chowdhury
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. John Q. Trojanowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Leslie M. Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The Parkinson’s Progression Marker Initiative

Corresponding author

Correspondence to Leslie M. Shaw.

Ethics declarations

Conflict of interest

Frasier is an employee of The Michael J. Fox Foundation for Parkinson’s Research. Marek has been a consultant for Pfizer Inc, GE Healthcare, Merck and Co, Eli Lilly and Co, Bristol-Myers Squibb, Piramal, Neotope Biosciences, and Neuro Phage Pharmaceuticals and has equity interest in Molecular NeuroImaging. Kieburtz has been a consultant for the National Institute of Neurological Disorders and Stroke, National Institutes of Health, US Food and Drug Administration, Veterans Affairs, Abbott, Acorda, Aptiv, Astra-Zeneca, Auspex, BiogenIdec, Biotie, Biovail, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ceregene, CHDI, Civitas, Clintrex, Cynapsus, Eli Lilly and Co, Endo, Impax, Intec, Ipsen, Isis, Knopp, Lundbeck, LZ Therapeutics, Medivation, Merck and Co, Merz, Neotope/Elan, Novartis, Orion, Otsuka, Pharma2B, Phytopharm, Roche, Siena Biotech, Sofinnova, Synagile, Synosia, Teva, UCB Pharma, Upsher-Smith, US World Meds, Vaccinex, Vectura, and Xenoport; and has performed legal consulting for Thompson Hine. Tanner has served on the scientific advisory boards of The Michael J. Fox Foundation for Parkinson’s Research and the National Spasmodic Dystonia Association; has been a consultant for Impax Pharmaceuticals and Adamas Pharmaceuticals; and is an employee of the Parkinson’s Institute and Clinical Center. Chowdhury is an employee of The Michael J. Fox Foundation for Parkinson’s Research. Shaw was previously a consultant for Fujirebio and collaborates on quality assessment activities as part of the Parkinson’s Progression Markers Initiative and as part of the Alzheimer’s Disease Neuroimaging Initiative. Leverenz has received compensation for consultation from Bayer Pharmaceuticals, Navidea Biopharmaceuticals, and Piramal Healthcare. Galasko serves as editor of Alzheimer’s Disease Research and Treatment; serves on data safety monitoring boards for Elan, Janssen, and Balance Pharmaceuticals; and is a consultant for Elan Pharmaceuticals; No other disclosures were reported.

Funding/Support

This work was supported by The Michael J. Fox Foundation for Parkinson’s Research, Abbott, Avid Radiopharmaceuticals, BiogenIdec, Covance, Elan, Eli Lilly and Co, F. Hoffman–LaRoche Ltd, GE Healthcare, Genentech, Glaxo Smith Kline, Merck and Co, Pfizer Inc, and UCB Pharma SA. Trojanowski and Chen-Plotkin were supported by core grant P50NS053488-05 from the Morris K. Udall Center of Excellence for Parkinson’s Disease Research. Irwin was supported by Training in Age-Related Neurodegenerative Diseases grant T32-AG000255 from the National Institute on Aging, National Institutes of Health. Singleton was supported by Grant Z01AG000949-06 from the Intramural Research Program, National Institute on Aging, National Institutes of Health. Ju-Hee was supported by Grant MRC 2014009392 from the National Research Foundation of Korea, Ministry of Science, ICT and Future Planning. Kieburtz has received grants and/or research support from the National Eye Institute, National Institute of Neurological Disorders and Stroke, National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Neurosearch, and Medication. Tanner has received grants and/or research support from Brin Foundation, James and Sharron Clark, Parkinson’s Institute and Clinical Center, Parkinson’s Disease Foundation, US Army Medical Research Acquisition Activity (Telemedicine and Advanced Technology Research Center—managed Neurotoxin Exposure Treatment Research Program), National Institute of Neurological Disorders and Stroke, Agency for Healthcare and Research Quality, and National Institute of Environmental Health Sciences. Galasko receives research support from the National Institutes of Health, and the Alzheimer’s Drug Discovery Foundation.

Additional information

The members of the Parkinson’s Progression Markers Initiative are listed in “Acknowledgments”.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 630 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kang, JH., Mollenhauer, B., Coffey, C.S. et al. CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study. Acta Neuropathol 131, 935–949 (2016). https://doi.org/10.1007/s00401-016-1552-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-016-1552-2

Keywords

Search

Navigation